The purpose of our investigation is to identify genes that confer an increased susceptibility to a psychiatric disorder or to a neuropharmacogenetic trait. To achieve this goal we use association and linkage mapping. We perform work on methods to detect unknown mutations. We also contribute to the collection of families needed to perform genetic experiments. Dopamine D2 Receptor (DRD2) gene: We have previously described three infrequent DNA variations in the DRD2 gene that predict substitutions in the amino acid sequence of the receptor (Gejman et al., 1994 JAMA). These variants, Val96 to Ala, Pro310 to Ser, and Ser311 to Cys, represent an interesting example of genetic heterogeneity of a human protein of great pharmacological importance. Expression of these missense variants in COS cells provided preliminary evidence the Ala96 and Ser310 might affect some binding properties of the receptor. Expression of variants in stable cell lines is in progress. Use of a blind protocol to establish the efficiency of denaturing gradient gel electrophoresis (DGGE) to detect mutations in fragments of various sizes: Mutational analysis methods, i.e., methods used to detect mutations in DNA are central to human molecular genetics. However, the power of these methods to detect mutations has been only occasionally evaluated in a systematic manner. We are using a blind protocol to quantify the power of detection of mutations by DGGE. Mutational Analysis of Monoamine Oxidase B Gene: A mutation in the MAO A gene has been described in members of a Dutch family with behavioral abnormalities and mild mental retardation. This mutation has not been found in other populations with comprobable phenotype. We have examined the exons and promoter of the MAO B gene for mutations in a Finnish population of violent impulsive alcoholics and found none.